1. Field of the Invention
The present invention relates to a carrier for use in sustained release preparation for providing a medicament, in particular, anticancer agent or antibiotic, available for medical treatment such as against cancer, neoplasm and osteomyelitis to an affected part of a patient""s body. The invention also relates to a method for manufacturing the carrier.
2. Description of the Related Art
Conventionally, those medicaments such as anticancer agent and antibiotic are available for medical treatment against cancer, neoplasm, or osteomyelitis. However, these medicaments more or less have grave side effects. Furthermore when dosing a patient""s body with any of these medicaments, in fact, only a small portion the dosed medicament reaches the affected part. To properly compensate for this, a novel method has been sought for selectively providing an optimum amount of the medicament to the affected part.
One method for delivering the medicament is a carrier for sustained release preparation capable of gradually releasing the medicament after burying it in the affected part of the patient""s body. For example, the Unexamined Published Japanese Patent Application No. 59-101145 discloses such a method which buries a porous ceramics carrier impregnated with medicament to provide an optimum amount of the prescribed medicament to the affected part. Another Unexamined Published Japanese Patent Application No. 61-47401 discloses a carrier for use in sustained release preparation consisting of calcium-phosphate ceramic carrier having a large specific surface area and containing absorbed medicament.
Another Unexamined Published Japanese Patent Application No. 62-6522 discloses a carrier for use in sustained release preparation consisting of porous alumina granules having spatial area internally filled with a medicament. In this case, the filled medicament gradually diffuses via pores of those porous alumina granules.
Another Unexamined Published Japanese Patent Application No. 1-197429 discloses such a carrier for use in sustained release preparation which, except for an aperture to permit impregnation of a medicament, covers the surface of porous ceramic body permitting impregnation of the medicament in pores each having 10 to 30 xcexcm of diameter by means of film having pores respectively having 10 xcexcm and less than of diameter and 300 xcexcm and less than of thickness.
These preceding Unexamined Published Japanese Patent Application No. 59-101145 and No. 61-47401 respectively disclose the art which initially requires a porous ceramic carrier to absorb the medicament, and then buries the porous ceramic carrier in the affected part of the patient body thereby permitting the medicament to be released from the porous ceramic carrier. Nevertheless, most of the medicament therein are not chemically absorbed in the porous ceramic carrier, but instead, medical ingredients are physically absorbed in this carrier. In consequence, immediately after being buried in the patient""s body, the medicament is quickly released from the porous ceramic carrier to result in the failure to constantly provide the medical ingredients to the affected part for an extended time. Even when varying the ratio and diameter of pores of the porous ceramic carrier, actually, it is quite difficult for this carrier to properly control the amount of the released medicament.
On the other hand, the carrier for use in sustained release preparation proposed by the Examined Published Japanese Patent Application No. 62-6522 is manufactured by blending deceptive pore forming material with alumina powder followed by a shaping process and a firing process. Distribution of pore diameter of porous carrier produced by executing those processes mentioned above is dependent on the dispersed condition of the pore forming material. Therefore, if the available pore forming material unevenly disperses, then, continuous pores are generated in a region where the pore forming material of the porous carrier is concentrated. In this case, a local average of pore diameter noticeably exceeds a total average of pore diameter of the porous carrier. Therefore, the pore diameter in this region affects the sustained release characteristic of the medicament by causing the carrier to fully release the medicament in a very short period of time.
As is clear from the above description, the carrier for use in sustained release preparation disclosed in the Examined Published Japanese Patent Application No. 62-6522 tend to vary the sustained release characteristic of the medicament among carriers according to the dispersed condition of the pore forming material. As a result, any of these conventional carriers quickly release the medicament to incur unwanted side effect to the patient""s body. On the other hand, any of these conventional carriers release a little amount of the medicament to nullify the effect of medical treatment.
On the other hand, the other carrier for sustained release preparation disclosed in the Unexamined Published Japanese Patent Application No. 1-197429 described above is buried in the affected part of the patient""s body without shutting off the aperture provided on the surface of the porous ceramic carrier. This in turn causes the medicament to leak out of the aperture by such an amount in excess of the prescribed dosage.
As described above, any of those conventional carriers for use in sustained release preparation cannot properly and fully exert the function of the carrier itself to stably provide the medicament to the affected part of the patient""s body for a long period of time.
The primary object of the invention is to provide a novel carrier for use in sustained release preparation, which is capable of selectively providing an optimum amount of a medicament to the affected part for a long period of time after being buried in the patient""s body.
Another object of the invention is to provide a novel carrier for use in sustained release preparation, which is capable of stably maintaining the sustained release characteristic of a medicament without varying it at all.
Another object of the invention is to provide a novel method for manufacturing a carrier for sustained release preparation to permit manufacturers to easily produce the carrier.
Specifically, the invention provides a novel carrier for use in sustained release preparation, which comprises a porous ceramic body having a cavity for retaining a medicament and which controls release of the medicament. The porous ceramic body is capsule-shaped and has pores extending inwardly of the outer periphery thereof, each of which has a diameter substantially proportional to the distance from a outer periphery of the porous ceramic body.
Furthermore the present invention provides a novel carrier for use in sustained release preparation, which comprises a porous ceramic body having a hollow for retaining a medicament and which controls release of the medicament, wherein the porous ceramic body is capsule-shaped and has pores, and has a pore rate which decrease toward to the outer periphery of the porous ceramic body.
Furthermore, the present invention provides a novel method for manufacturing a carrier for use in sustained release preparation, which carrier comprises a porous ceramic body having a hollow for retaining a medicament and controls release of the medicament. The method comprises a step of preparing a raw material ceramics slurry, a step of preparing a preformed body containing a hollow by causing the raw material ceramic slurry to adhere on an inner wall surface of a solvent-absorbable mold, a step of firing the preformed body, thereby obtaining the porous ceramic body is capsule-shaped and has pores, each of which has a diameter substantially proportional to the distance from a outer periphery of the porous ceramic body.
Furthermore, the present invention provides a novel method for manufacturing a carrier for use in sustained release preparation, which carrier comprises a porous ceramic body having a hollow cavity for retaining a medicament and controls release of the medicament. The method comprises a step of preparing a slurry of the raw material for forming the porous ceramic body, a step of preparing a preformed hollow body containing a cavity by coating the raw material ceramic slurry on an inner wall surface of a solvent-absorbable mold, a step of firing the preformed body, thereby obtained the porous ceramic body is capsule-shaped and has pores, and has a pore rate which decreases toward to the outer periphery of the porous ceramic body.
Next, details of the carrier for use in sustained release preparation and the related manufacturing methods are described below.
The carrier for use in sustained release preparation of the present invention has a cavity for retaining a medicament inside of a porous ceramic body which is capable of constantly releasing an optimum amount of the medicament. Therefore, the medicament can be retained in the cavity by immersing the carrier in solution of the medicament. When the carrier internally retaining the medicament is buried in a patient""s body, the medicament is gradually released through pores of the porous ceramic body, thereby constantly releasing an optimum amount of the medicament for a long period of service life.
In the carrier of the present invention, it is also particularly preferred to use such a porous ceramic body having the pore diameter corresponding to the peak value of the distribution thereof to decrease toward to the outer periphery of the porous ceramic body.
Note that the distribution of pore diameter means a frequency of appearance of the pore against the particular pore diameter thereof, the porous are contained into the region of the porous ceramic body, which exist at the same distance from the external surface of the porous body and of which thickness is sufficiently thin compared to thickness of the all porous body.
Substantially, in the vicinity of the outer periphery, the porous ceramic body is devoid of large pores, but instead, all pores are dense structure. Owing to this structural advantage, the porous ceramic body is capable of retaining the medicament in the hollow thereof for a long period of service life, and yet, the porous ceramic body can maintain the released amount of the medicament constant.
In the present invention, the released amount of the medicament can properly be controlled through varying the medicament-permeability and diffusion characteristic of the porous ceramic body by means of varying the pore ratio, the pore diameter, and thickness of the porous ceramic body.
Material for composing the porous ceramic body of the present invention may be selected from calcium phosphate containing distinct bioaffinity, alumina, zirconia or mixture of these. In particular, the calcium phosphate ceramics is ideally suited for preparing the carrier for use in sustained release preparation of the present invention particularly in the case of burying it in the bone tissue of a patient for medically treating osteometitis.
As is apparent from the above description, according to the carrier for use in sustained release preparation of the present invention, when the carrier retaining the medicament is buried in the affected part of the patient""s body, the medicament is gradually released via pores of the porous ceramic body, and thus, an optimum amount of the medicament can directly and selectively be provided to the affected part. As a result, the effect of medical treatment can be fully achieved merely by internally providing a slight amount of the medicament, and yet, effectively minimize grave side effects.
On the other hand, according to the method of manufacturing the carrier for use in sustained release preparation of the present invention, a slurry of the raw material for the ceramic is deposited on the inner wall surface of a solvent-absorbable mold to cause water in slurry to be absorbed in the mold very quickly, thus producing a preformed body having a hollow center.
Also, according to the method of manufacturing the carrier for use in sustained release preparation of the present invention, a plurality of parts may individually be formed at the initial step before preparing a preformed body by combining these parts with each other. For example, when making up a preformed body, initially, semispherical parts are molded, and then these parts are bonded together to complete a preformed body.
As is clear from the above description, according to the method of manufacturing the carrier for use in sustained release preparation of the present invention, the carrier can easily be manufactured.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out in the appended claims.